The overall goal is to determine whether genes which predispose to certain childhood tumors are associated with an abnormal in vitro response to radiation and/or chemical mutagens/carcinogens. We have ascertained a series of unique patients who seem to have a heritable tumor, based on family studies, bilateral tumors, or constitutional chromosome deletions, and who have developed spontaneous or radiation related second tumors. In several families, multiple family members have developed radiation related tumors. For each distinct subgroup of patients, including those with heritable retinoblastoma, nevoid basal cell carcinoma syndrome, sarcoma/breast cancer/brain tumor familial cancer syndrome, neurofibromatosis, and Wilms' tumor, we wish to determine whether there is any underlying genetic instability or abnormal response to radiation or chemical carcinogens in fibroblasts or peripheral blood. We further hope to determine whether there is a common site of inherited or acquired chromosome instability in terms of deletion, in peripheral blood, fibroblasts, and/or tumor from individuals with retinoblastoma and Wilms' tumor. Positive findings in any patient group, if confirmed as being related to the cancer predisposing gene, would provide for development of a system to identify individuals genetically predisposed to specific tumors, and those most susceptible to certain environmental carcinogens, including those at greatest risk of developing new tumors over time. This information could provide rationale for alteration in cancer therapy or follow-up. Consistent positive findings could provide the background for development of hypotheses regarding mechanisms of susceptibility, pretesting in vitro means of reversing the above observed susceptibility, and further investigating the nature of the genes predisposing to childhood cancer.